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Phosphorylated insulin like growth factor

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https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#1
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28521459/cisplatin-regulates-cell-autophagy-in-endometrial-cancer-cells-via-the-pi3k-akt-mtor-signalling-pathway
#2
Qiongyan Lin, Yifeng Wang, Dunjin Chen, Xiujie Sheng, Juan Liu, Hanzhen Xiong
Endometrial cancer is the most common gynaecological malignancy encountered in developed countries and the second most common in the developing world. The five-year survival rate of patients with endometrial cancer diagnosed at a late stage is <30%. Therefore, it is critical to develop a suitable chemotherapeutic regimen for late-stage endometrial cancer. Cisplatin (CDDP) is a first-line chemotherapeutic drug for endometrial cancer chemotherapy. The present study investigated the molecular mechanism underlying the effect of CDDP on endometrial cancer from the perspective of cell autophagy...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520765/an-integrative-analysis-of-tissue-specific-transcriptomic-and-metabolomic-responses-to-short-term-dietary-methionine-restriction-in-mice
#3
Sujoy Ghosh, Laura A Forney, Desiree Wanders, Kirsten P Stone, Thomas W Gettys
Dietary methionine restriction (MR) produces a coordinated series of transcriptional responses in peripheral tissues that limit fat accretion, remodel lipid metabolism in liver and adipose tissue, and improve overall insulin sensitivity. Hepatic sensing of reduced methionine leads to induction and release of fibroblast growth factor 21 (FGF21), which acts centrally to increase sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has direct effects in adipose to enhance glucose uptake and oxidation...
2017: PloS One
https://www.readbyqxmd.com/read/28507717/dynamic-structural-and-thermodynamic-basis-of-insulin-like-growth-factor-1-kinase-allostery-mediated-by-activation-loop-phosphorylation
#4
Yaozong Li, Kwangho Nam
Despite the importance of kinases' catalytic activity regulation in cell signaling, detailed mechanisms underlying their activity regulation are poorly understood. Herein, using insulin-like growth factor 1 receptor kinase (IGF-1RK) as a model, the mechanisms of kinase regulation by its activation loop (A-loop) phosphorylation were investigated through molecular dynamics (MD) and alchemical free energy simulations. Analyses of the simulation results and free energy landscapes determined for the entire catalytic cycle of the kinase revealed that A-loop phosphorylation affects each step in the IGF-1RK catalytic cycle, including conformational change, substrate binding/product release and catalytic phosphoryl transfer...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28507342/effects-of-dietary-methionine-on-breast-muscle-growth-myogenic-gene-expression-and-igf-i-signaling-in-fast-and-slow-growing-broilers
#5
Chao Wen, Xueying Jiang, Liren Ding, Tian Wang, Yanmin Zhou
This study investigated the responses of fast- (FG) and slow- (SG) growing broilers to dietary methionine (Met) status. The broilers were subjected to low (LM, 0.38 and 0.28 g/100 g), adequate (AM, 0.51 and 0.42 g/100 g) and high (HM, 0.65 and 0.52 g/100 g) Met during 1-21 and 22-42 d, respectively. Compared with the LM diets, the AM and HM diets increased body weight gain only in the FG broilers. The HM diets increased breast muscle yield only in the FG broilers, although insulin-like growth factor-I (IGF-I) concentration was increased in both strains of broilers...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28497370/igf2bp1-a-novel-binding-protein-of-p38-mapk
#6
Jacob Rini, Moorthy Anbalagan
Signal transduction pathways control various biological processes in cells leading to distinct cellular functions. Protein-protein interactions and post-translational modifications are the physiological events that occur in signaling pathway. p38 MAPK are known to be involved in regulating wide range of cellular processes by interacting and activating relevant signaling molecules by means of phosphorylation. Deregulation of p38 MAPK is associated with various pathological conditions. In order to get an insight into the role played by p38 MAPK in cellular signaling, studies were carried out to identify proteins that interact with p38 MAPK...
May 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28495324/biology-of-the-somatotroph-axis-after-the-pituitary
#7
Ron G Rosenfeld, Vivian Hwa
Normal growth requires that pituitary-secreted growth hormone (GH) bind to its specific receptor and activate a complex signaling cascade, leaving to production of insulin-like growth factor-I (IGF-I), which, in turn, activates its own receptor (IGF1R). The GH receptor (GHR) is preformed as a dimer and is transported in a nonligand bound state to the cell surface. Binding of GH to the GHR dimer, results in a conformational change of the dimer, activation of the intracellular Janus Kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription (STAT) 5B...
May 8, 2017: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28472298/adiponectin-stimulates-lipid-metabolism-via-ampk-in-rabbit-blastocysts
#8
Maria Schindler, Mareike Pendzialek, Katarzyna Joanna Grybel, Tom Seeling, Jacqueline Gürke, Bernd Fischer, Anne Navarrete Santos
STUDY QUESTION: How does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts? SUMMARY ANSWER: In a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover. WHAT IS KNOWN ALREADY: Although studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5'-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available...
May 4, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28468775/targeting-insulin-receptor-in-breast-cancer-using-small-engineered-protein-scaffolds
#9
Jie Ying Chan, Benjamin J Hackel, Douglas Yee
Insulin receptor (InsR) and the type I insulin-like growth factor (IGF1R) are homologous receptors necessary for signal transduction by their cognate ligands insulin, insulin-like growth factor-I and -II (IGF-I and IGF-II). IGF1R monoclonal antibodies, intended to inhibit malignant phenotypic signaling, failed to show benefit in patients with endocrine-resistant tumors in phase III clinical trials. Our previous work showed that in tamoxifen-resistant cells IGF1R expression was lacking but InsR inhibition effectively blocked growth...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28468523/non-essential-and-branched-chain-amino-acids-differentially-regulate-insulin-like-growth-factor-binding-protein-1-production-and-phosphorylation-in-hepg2-cells
#10
Kei Tanaka, Keiji Sakai, Miho Matsushima, Yukiko Matsuzawa, Tomoko Izawa, Yoichi Kobayashi, Mitsutoshi Iwashita
Deprivation of branched-chain amino acids (BCAAs) induces insulin-like growth factor binding protein-1 (IGFBP-1) production in HepG2 cells, while the role of non-essential amino acids (NEAAs) remains unknown. We investigated changes in IGFBP-1 production and phosphorylation induced by NEAAs and also examined its significance on IGF-I activity in HepG2 cells. We demonstrated that decreased BCAAs and increased NEAAs stimulated phosphorylated IGFBP-1 secretion. We also revealed that decreased BCAA-to-NEAA ratios enhanced phosphorylated IGFBP-1 secretion, while changes in the total amount of amino acids (AAs) had no effect...
May 4, 2017: Growth Factors
https://www.readbyqxmd.com/read/28460483/a-bispecific-enediyne-energized-fusion-protein-targeting-both-epidermal-growth-factor-receptor-and-insulin-like-growth-factor-1-receptor-showing-enhanced-antitumor-efficacy-against-non-small-cell-lung-cancer
#11
Xiao-Fang Guo, Xiao-Fei Zhu, Hai-Ying Cao, Gen-Shen Zhong, Liang Li, Bao-Guo Deng, Ping Chen, Pei-Zhen Wang, Qing-Fang Miao, Yong-Su Zhen
Epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) both overexpressed on non-small cell lung cancer (NSCLC) and are known cooperatively to promote tumor progression and drug resistance. This study was to construct a novel bispecific fusion protein EGF-IGF-LDP-AE consisting of EGFR and IGF-IR specific ligands (EGF and IGF-1) and lidamycin, an enediyne antibiotic with potent antitumor activity, and investigate its antitumor efficacy against NSCLC. Binding and internalization assays showed that EGF-IGF-LDP protein could bind to NSCLC cells with high affinity and then internalized into cells with higher efficiency than that of monospecific proteins...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460125/how-protein-kinase-a-activates-canonical-tyrosine-kinase-signaling-pathways-to-promote-granulosa-cell-differentiation
#12
Nathan C Law, Elyse M Donaubauer, Anthony J Zeleznik, Mary Hunzicker-Dunn
Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We sought to elucidate the mechanism by which PKA, a Ser/Thr kinase, intersected the PI3K/AKT and MAPK/ERK pathways that are canonically activated by receptor tyrosine kinases (RTKs). Our results show that for both of these pathways, the RTK is active in the absence of FSH yet signaling down the pathways to commence transcriptional responses requires FSH-stimulated PKA activation...
April 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28455310/exercise-induced-modification-of-the-skeletal-muscle-transcriptome-in-arabian-horses
#13
Katarzyna Ropka-Molik, Monika Stefaniuk-Szmukier, Kacper Żukowski, Katarzyna Piórkowska, Monika Bugno-Poniewierska
It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T0 (untrained horses), T1 (horses after intense gallop phase) and T2 (horses at the end of racing season), 23 samples in total...
April 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28454094/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#14
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440057/overcoming-linsitinib-intrinsic-resistance-through-inhibition-of-nuclear-factor-%C3%AE%C2%BAb-signaling-in-esophageal-squamous-cell-carcinoma
#15
Junzhou Wu, Kaiyan Chen, Fanrong Zhang, Jiaoyue Jin, Nan Zhang, Dan Li, Lisha Ying, Wei Chen, Herbert Yu, Weimin Mao, Dan Su
The aim of this study is to evaluate the efficacy of insulin-like growth factor 1 receptor (IGF-1R) inhibitor Linsitinib, in esophageal squamous cell carcinoma (ESCC), and to characterize special biomarker to screen Linsitinib-sensitive patients as well as explore the molecular-resistant mechanism to Linsitinib in ESCC. Our study evaluated the sensitivity of insulin-like growth factor 1 receptor (IGF-1R) inhibitor, Linsitinib in ESCC cells with MTT assay. After Linsitinib treatment, the expressions of downstream signaling molecules and apoptosis pathways were measured by western blot...
April 24, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28433890/il-37-induces-autophagy-in-hepatocellular-carcinoma-cells-by-inhibiting-the-pi3k-akt-mtor-pathway
#16
Ting-Ting Li, Di Zhu, Tong Mou, Zhen Guo, Jun-Liang Pu, Qing-Song Chen, Xu-Fu Wei, Zhong-Jun Wu
Autophagy is an intracellular "self-eating" process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown...
April 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28421341/insufficient-activation-of-akt-upon-reperfusion-because-of-its-novel-modification-by-reduced-pp2a-b55%C3%AE-contributes-to-enlargement-of-infarct-size-by-chronic-kidney-disease
#17
Toshiyuki Tobisawa, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Yukishige Kimura, Satoko Ishikawa, Hidemichi Kouzu, Keitaro Nishizawa, Hideaki Yoshida, Tetsuji Miura
Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28410230/insulin-growth-factor-binding-protein-2-mediates-the-progression-of-lymphangioleiomyomatosis
#18
Xiangke Li, Xiaolei Liu, Linda Zhang, Chenggang Li, Erik Zhang, Wang Ma, Qingxia Fan, Jane J Yu
Lymphangioleiomyomatosis (LAM) is a progressive pulmonary disease that almost exclusively affects women. LAM cells migrate to the lungs, where they cause cystic destruction of lung parenchyma. Mutations in TSC1 or TSC2 lead to the activation of the mammalian target of rapamycin complex-1, a kinase that regulates growth factor-dependent protein translation, cell growth, and metabolism. Insulin-like growth factor binding protein 2 (IGFBP2) binds insulin, IGF1 and IGF2 in circulation, thereby modulating cell survival, migration, and invasion in neoplasms...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389416/cell-surface-grp78-facilitates-hepatoma-cells-proliferation-and-migration-by-activating-igf-ir
#19
Yancun Yin, Chen Chen, Jinliang Chen, Renhui Zhan, Qiang Zhang, Xiaoyan Xu, Defang Li, Minjing Li
The 78kDa glucose regulated protein (GRP78) is a multifunctional chaperone that is involved in a variety of cellular processes. Insulin like growth factor I receptor (IGF-IR) often aberrant expresses in many types of tumor cells. The IGF-IR signaling plays key roles in carcinogenesis and maintenance of the malignant phenotype. The crosstalk between GRP78 and IGF-IR molecules has not well been illuminated. Here, we demonstrated a reciprocal regulation of GRP78 expression and IGF-IR pathway activation. IGF-I induced GRP78 expression in hepatoma cells...
April 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28383811/hsf1-phosphorylation-by-erk-gsk3-suppresses-rnf126-to-sustain-igf-iir-expression-for-hypertension-induced-cardiomyocyte-hypertrophy
#20
Chih-Yang Huang, Fa-Lun Lee, Shu-Fen Peng, Kuan-Ho Lin, Ray-Jade Chen, Tsung-Jung Ho, Fu-Jen Tsai, V Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT1 R)...
April 6, 2017: Journal of Cellular Physiology
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